The long-term goal of this proposal is to characterize the function of NIL- 16, a neuron-specific PDZ protein that is also a precursor for the cytokine, IL-16. In the mouse, NIL-16 is expressed exclusively in neurons of the hippocampus and cerebellum, where it can be cleaved by caspase-3 to liberate IL-16. This study will focus on NIL-16's potential dual function. First, it will investigate its role as a scaffolding protein that influences currents through ion channels that bind to the PDZ domains of NIL-16. Second, it will determine what role IL-16 plays in synaptic physiology in hippocampus and cerebellum. SPECIFIC AIM 1 will use whole cell patch clamping to determine whether NIL-16 affects ion currents when cotransfected into COS-7 cells with specific ion channels or receptors. In SPECIFIC AIM 2 patch clamping will be used to assess channel properties of cultured cerebellar granule neurons derived from NIL-16- null mice or their wild type littermates. In SPECIFIC AIM 3, the effects of IL-16 on LTP in hippocampal and cerebellar slices will be determined. Together, these studies will shed light on a novel mechanism for coordinating signaling in the nervous system.